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Increased Liver Enzymes Deteriorates Glucose Tolerance

Increased levels of the liver enzyme GGT are an independent predictor of metabolic outcome, particularly of the development of impaired glucose tolerance or diabetes. Investigators with the Mexico City Diabetes Study, a population-based survey of type 2 diabetes and cardiovascular risk factors, tested the theory that four liver enzymes linked to liver dysfunction (AST, ALT, ALP, and GGT) may predict diabetes in a cohort of 1,441 adults free of evidence of hepatitis B or C virus infection or active liver damage who consumed less than 250 grams of alcohol per week.

During 7 years of follow up, 94 subjects developed diabetes and 93 developed impaired glucose tolerance.

In univariate analysis, each of the four enzymes (AST, ALT, ALP, and GGT) was related to most features of the metabolic syndrome, Dr. Monica Nannipieri from the University of Pisa in Italy and colleagues report.

In multivariate analysis adjusted for sex, age, weight and fat distribution, alcohol intake, lipids and BP, higher ALT and GGT levels were significantly associated with both impaired glucose tolerance and diabetes (p < 0.01), whereas ALP was associated with diabetes only (p = 0.0004) and AST with impaired glucose tolerance only (p = 0.0001).

However, only elevated GGT was associated with all of the features of the metabolic syndrome and significantly and independently predicted either impaired glucose tolerance or diabetes, even after controlling for well known-predictors of deteriorating glucose tolerance. The odds ratio for these outcomes was 1.62 for the top quartile of GGT versus lower quartiles.
"The current data thus consolidate the preeminence of GGT as an independent predictor of metabolic outcome," Dr. Nannipieri and colleagues write.

"As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress," the investigators suggest.

"Because oxidative stress with the attendant low-grade inflammation is implicated in a number of pathological conditions, including aging, atherosclerosis, and diabetes, one could speculate that chronic mild elevations in GGT may predispose to diabetes by mediating/inducing oxidative stress," Dr. Nannipieri and colleagues conclude.
Diabetes Care 2005;28:1757-1762.

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